Unravelling the mechanisms of tumor heterogeneity and budding in colorectal cancer.

Colorectal cancer (CRC) is wordwide the 3rd leading cause of cancer related death. While some process has been made in therapy since the introduction of EGFR targeted therapy, there is still a high need for risk stratification to better predict prognosis and for more effective and individualized therapy strategies. This project aims to contribute to a better understanding of CRC by investigating 2 features that not only play an important role in tumor biology but also may have a major impact on diagnosis and therapy: tumor heterogeneity and budding. Budding is the process in which individual or small groups of cells detach from the main tumor and invade the stroma, and is associated with lymphovascular invasion, metastasis, and poor prognosis. Tumor heterogeneity is the presence of multiple clones within one tumor, and is a major challenge for targeted therapy as tumour cell clones that were not detected with a classic molecular test may persist after treatment against the originally tested target, increasing risk for resistance and relapse. This project aims to unravel the mechanism of both budding and tumor heterogeneity in CRC by means of gene expression profiling, mutation analysis, in vitro tests, and analysis of the immune response and angiogenesis. The newly acquired insights will shed new light on CRC biology in order to optimize and improve the current diagnostic and therapeutic protocols.